In this paper I present a model of rational belief change, and I show how to use it to obtain a better insight into the debate about the nature of pneumococcal transformation, genes and DNA that took place in the forties, as a result of Oswald T. Avery’s work. The model offers a particular elaboration of the concept of inference to the best explanation, along decision theoretic lines. Within this framework, I distinguish different senses in which Avery’s team can be said to have proceeded with caution, thus throwing some light upon a persistent source of disagreement among researchers in the history of genetics. In addition, I explain why we are entitled to say that rival parties such as physicist Maclyn McCarty and biochemist Alfred Mirsky were epistemically rational, in spite of the fact that they reached different conclusions on the basis of the same evidence